Abstract
Solvent shielding of the amide hydrogen bond donor (NH groups) through chemical modification or conformational control has been successfully utilized to impart membrane permeability to ...macrocyclic peptides. We demonstrate that passive membrane permeability can also be conferred by masking the amide hydrogen bond acceptor (>C = O) through a thioamide substitution (>C = S). The membrane permeability is a consequence of the lower desolvation penalty of the macrocycle resulting from a concerted effect of conformational restriction, local desolvation of the thioamide bond, and solvent shielding of the amide NH groups. The enhanced permeability and metabolic stability on thioamidation improve the bioavailability of a macrocyclic peptide composed of hydrophobic amino acids when administered through the oral route in rats. Thioamidation of a bioactive macrocyclic peptide composed of polar amino acids results in analogs with longer duration of action in rats when delivered subcutaneously. These results highlight the potential of O to S substitution as a stable backbone modification in improving the pharmacological properties of peptide macrocycles.
•Dengue virus serotypes were tested in 4963 samples collected across India in 2018.•DENV-2 was the most prevalent serotype in many states of India.•Two genotypes of DENV-1 (I and V) were ...circulating.•Two lineages of DENV-2 genotype IV were circulating.•DENV-3 genotype III and DENV-4 genotype-I were circulating.
A retrospective study was undertaken to investigate the circulating dengue virus (DENV) serotypes and genotypes in India in 2018.
In total, 4963 samples referred to virus research diagnostic laboratories (n=21), the Indian Council of Medical Research-National Institute of Virology (ICMR-NIV) and ICMR-NIV field units (n=2) for diagnosis of dengue in 2018 were tested using a real-time reverse transcription polymerase chain reaction assay for the presence of DENV serotypes. Representative samples were sequenced for the envelope (E) gene.
Regional diversity was observed with regard to the dominant circulating serotypes. DENV-2 was found to be the most common serotype in many states. Thrombocytopenia, petechiae and malaise were associated with DENV-2 infection. Phylogenetic analyses of DENV E gene sequences revealed the circulation of genotypes I and V of DENV-1, two lineages of DENV-2 genotype IV, DENV-3 genotype III and DENV-4 genotype I.
This study found regional differences in the prevalence of circulating DENV serotypes in India, and provides baseline data for continuous molecular surveillance. Molecular surveillance may have implications for predicting large-scale outbreaks of dengue if regional shifts in the predominantly circulating serotypes and genotypes are detected during the early phase of the dengue season.
Ternary oxide glass system of chemical composition of 80B2O3–(20-x)Na2O–xCdO (where x=0, 2, 4, 6, 8, 10, 12, 14mol%) have been prepared by conventional melting and quenching method. The micro ...structural and morphological investigation of synthesized glass samples were carried out by using XRD, FE-SEM. The supporting physical and composition dependent properties such as experimental and theoretical density, molar volume, oxygen packing density, ionic concentration, interionic distance and polaron radius were determined. Density of glass samples increases, while molar volume decreases with the increasing cadmium oxide concentration from 0 to 14mol%. X-ray diffraction profiles and FE-SEM images confirmed amorphous nature of investigated glass samples. Elemental analysis and information about the chemical composition of glass matrices have been ascertained by using EDS spectra. The interpretation of functional groups BO3 and BO4 units present in the oxide glass was simulated by using deconvoluted Raman spectra and FTIR spectroscopy. BO stretching, metal cation active vibrational modes and bending vibrations of BOB linkage in borate glass network are cross verified by using FTIR and Raman spectroscopy.
•CdO doped Sodium-Borate glass samples are prepared by melt quenching method.•Physical, structural study and network analysis of sodium borate glass•FTIR and Raman spectroscopic properties were evaluated for the prepared glass.•Analysis of Raman spectra of glass is done by using deconvolution method.•The formation of glassy networks and their modification due to varying CdO concentration
Quaternary alkali borate glass matrix doped with CdO (0, 2, 4, 6, 8, 10 mol%) have been prepared by using conventional melting and quenching technique. For these glass systems structural properties ...were investigated by using X-ray diffraction, FE-SEM, EDS, FTIR and Raman spectroscopy characterization techniques. X-ray diffraction pattern and FE-SEM studies confirms the amorphous nature of prepared oxide glass. The optical absorption studies were done by using UV–Vis spectroscopy technique at room temperature. The physical parameters of all the glass samples were evaluated with respect to the composition, such as bulk density (ρ), average molar mass (M), molar volume (Vm), ionic concentration (N), interionic distance (ri). They exhibit the non-linearity supporting evidence for the borate glass network modification. Investigations of FTIR and Raman spectroscopy of prepared glass samples have been employed to confirm the role of oxides in the formation of glass network. These glasses are made up from converting BO3 to BO4 units without increasing the concentration of non-bridging oxygen. Experimental fraction of 4-coordinated boron atoms expressed by the parameter N4 was calculated and represented with the addition of concentration of CdO (mol%). The optical absorption studies revealed that the average refractive index (nav), optical band gap energy (Eg) nonlinearly increases. The electronic polarizability and optical basicity of the oxide ion (αO2−), as function of refractive index and optical band gap energy were also examined.
•CdO doped alkali Borate glass samples are prepared by melt quenching method.•Physical, structural and optical properties and network analysis of TM doped alkali borate glass.•Different optical property studies were done with UV–vis spectroscopy and theoretical approach.•Analysis of Raman spectra of glass is done by using deconvolution method.•The correlation of glassy network formation and their modification due to varying CdO concentration.
This paper reports the synthesis of three new derivatives of 2,4,5-trinitroimidazole namely, 1-methyl-2,4,5-trinitroimidazole (
III), 1-carboethoxy-2,4,5-trinitroimidazole (
V) and ...1-picryl-2,4,5-trinitroimidazole (
VII). The title compounds (
III) and (
V) were synthesized by the nitration of 1-methyl-/1-carboethoxy-(2,4,5-triiodoimidazole) (
II and
IV) with fuming nitric acid at 0
°C and (
VII) was synthesized by condensation of 2,4,5-triiodoimidazole (
I) with picryl chloride to obtain 1-picryl-2,4,5-triiodoimidazole (
VI) followed by its nitration with fuming nitric acid at 0
°C. The synthesized compounds have been characterized by elemental analysis, spectral and thermal techniques. The thermolysis studies using TG-DTA revealed exothermic decomposition of the nitroimidazoles (
III,
V and
VII) with
T
max in the temperature range of 196–225
°C. The energy of activation obtained for these compounds was in the range 150–170
kJ/mol. The sensitivity data obtained for the newly synthesized compounds (
III,
V and
VII) indicated their safe nature towards external stimuli (
h
50%
>
100
cm; friction
>
36
kg) and could be potential candidates for low vulnerable applications in the futuristic systems. The theoretically predicted performance parameters suggest that 1-methyl-2,4,5-trinitroimidazole (
III), exhibits higher velocity of detonation (VOD: 8.8
km/s) compared to compounds
V and
VII (VOD: 7.6 and 8.41
km/s, respectively).
The ferrite compositions Ni
1−
x
Cd
x
Fe
2O
4 with
x
=
0.2, 0.4, 0.6 were synthesized through the self-propagating auto combustion method. The powders were characterized using XRD for phase ...identification, crystallite size and lattice parameter calculation. It reveals the presence of cubic spinel structure of ferrites with crystallite size of 15–20
nm. SEM micrographs show uniform distribution of ferrite particles with some agglomeration. The lattice parameter is found to increase with increase in cadmium content. The IR absorption spectra show two bands corresponding to tetrahedral and octahedral vibrations. The dc electrical resistivity measured as a function of temperature from room temperature to 700
°C shows the semiconducting nature of the ferrites. The room temperature resistivity was found to be of the order of 10
8
Ω
m. The drift mobility is found to decrease with increase in cadmium content. The linear variation of AC conductivity with frequency confirms small polaron type of conduction mechanism. The dielectric properties were studied in the frequency range 20
Hz to 1
MHz. Dielectric constant shows dispersion in the lower frequency region and remains almost constant at higher frequencies. The variation of loss tangent with frequency is similar to that of the variation of dielectric constant with frequency. The present ferrites are well suitable for the applications in multi layer chip inductor (MLCI) due to low temperature sinterability and low magnetic loss.
India witnessed dengue outbreaks during 2017 in different parts with more than 180000 cases. There is no data on the serotypes/genotypes of dengue virus (DENV) associated with the 2017 outbreak ...season. The present study investigated DENV circulating in Pune and Nashik regions of Maharashtra, Western India at molecular level. IgM negative samples that were collected before 6th post onset days of illness were tested for DENV RNA and serotyped by real time RT-PCR based methods. Representative samples of each serotype were processed for virus isolation and envelope (E) gene sequencing. Among the 472 samples tested for DENV serotypes from Nashik, DENV-1 was observed in 36.2%, DENV-2 in 12.9%, DENV-3 in 35.4%, DENV-4 in 8.0%, and multiple serotypes in 7.4% of the samples respectively. In Pune region, among the 109 samples tested for DENV serotypes, DENV-1 was observed in 27.5%, DENV-2 in 11.0%, DENV-3 in 52.3%, DENV-4 in 4.6%, and multiple serotypes in 4.6% of the samples respectively. Comparison of serotype distribution from 2009 to 2017 from the Pune region revealed the emergence of DENV-3 as the dominant serotype followed by DENV-1 in 2017. In the Nashik region, both DENV-1 and DENV-3 were predominant in 2017. Phylogenetic analyses revealed co-circulation of American African (AM/AF) and Asian genotypes of DENV-1. DENV-1 Asian genotype was detected for the first time in the region. No genotype changes were observed for DENV-2 (cosmopolitan genotype), DENV-3 (genotype III) and DENV-4 (genotype I). For DENV-3, a unique amino acid substitution (I380T) was observed in the domain III of E protein of 2017 isolates and was not observed in earlier DENV-3 genotype III isolates. To conclude, the results suggest the emergence of DENV-1 with circulation of both Asian and AM/AF genotypes and DENV-3 with unique amino acid substitutions in Pune and Nashik regions. The study underscores the need for continuous molecular monitoring at a large scale to detect the changes in DENV serotypes/genotypes that might have implications for earlier prediction of dengue outbreaks and designing dengue vaccines and predicting its efficacy.
•DENV-1 and DENV-3 were the dominant serotypes in 2017 from Pune and Nashik regions, Western India.•For DENV-1, both Asian and American/Afrcian genotypes were circulating.•DENV-1 Asian genotype was detected first time in the region.•DENV-3 genotype III was circulating with a unique amino acid substitution (I380T) in EDIII.•The study underscores the need for continuous molecular surveillance of DENV serotypes/genotypes.
This study explored the influence of moringa (Moringa oleifera; MO) foliage supplementation on in vitro ruminalgas production kinetics and substrate degradation in cattle. In vitro fermentation study ...was carried out with twotypes of substrates, viz. wheat straw (WS) and WS plus concentrate mixture (CM; 60:40) in cattle rumen inoculum.The MO was incorporated to both the substrates at 0, 5, 10, 20, 30, 40 and 50% levels of total dry matter. Thesubstrates were incubated up to 24 h and substrate degradation was measured. The in vitro gas production kineticswas performed with 8 different (0, 5, 10, 20, 30, 40, 50 and 100%) levels of MO with WS substrate and incubatedat 0, 3, 6, 9, 12, 24, 36, 48 and 72 h. The MO addition increased the total gas volume (ml/200 mg) up to 50% level,though, it was analogous when WS and CM based substrate was used. The truly degradable organic matter in rumen (TDOMR) was increased with MO supplementation from 10% onwards. The microbial biomass production (MBP) and partitioning factor (PF) were higher on 30% onwards MO levels. Addition of MO increased the gas production at 24 h from 30% onwards, however, cumulative gas production at 72 h was higher in control (CON). The potential gas production (b) was higher for CON than MO substrates. Fractional rate of fermentation (c) increased from 10 to 100% MO levels. The half time (t1/2) of gas production was substantially reduced with MO supplementation. The volume of gas at t1/2 was significantly lower at 30%. TDOMR was analogous amongst the treatments, however, MBP and PF were higher at 30% level relative to 10 and 20% MO levels. Hence, it may be deduced that supplementation of moringa foliage to cereal straw-based substrate considerably improved the gas production, fractional rate of fermentation, TDOMR, MBP and PF in cattle inoculum.
This paper deals with the influence of a biocompatible surface coating layer on the structural, morphological and colloidal and magnetic properties of the MnZnFe2O4 nanoparticles. A series of the ...MnZnFe2O4 magnetic nanoparticles were synthesized by simple cost-effective co-precipitation technique. Herein, it is found that starch plays an important role in the colloidal stability, dispersibility and the heating efficiency of MNPs. Samples of the resultant magnetic fluid were examined using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES), X-ray diffraction (XRD), transmission electron microscopy (TEM), Field emission scanning electron microscopy (FESEM), dynamic light scattering, zeta potential measurements, Vibrating sample magnetometry (VSM) and induction heating studies. The average size of the MnZnFe2O4 and MnZnFe2O4@starch nanoparticles estimated by TEM technique was found to be in the range of 12–15 nm. Magnetometry measurements indicate that superparamagnetic like nature with negligible coercivity and remanence for any of sample. Induction heating efficiency of MnZnFe2O4 nanoparticles under alternating magnetic field was studied by means of specific absorption rate (SAR) measurements, and compared with starch functionalized MnZnFe2O4 nanoparticles. In vitro cytotoxicity on human lung cancer cells studies reveal that tolerable dose rate for MNPs can be significantly high and particles are less toxic in nature. Based on these characterizations of the samples it is suggested that the MnZnFe2O4 ferrites may be a potential candidate for hyperthermia application.
Cell viability Vs Concentration for bare and starch functionalized MnZnFe2O4 MNPs. Display omitted
•Surface functionalization of MnZnFe2O4 nanoparticles with starch.•Improved efficiency of magnetic fluid hyperthermia treatment for starch functionalized NPs (also enhanced SAR).•The heating ability observed at low concentration.•Good biocompatibility on human lung carcinoma cells for functionalized MnZnFe2O4@starch nanoparticles.
The optimal imaging paradigm for endovascular thrombectomy (EVT) patient selection in early time window (0-6 hours) treated acute ischemic stroke patients remains uncertain. We aimed to compare ...post-EVT outcomes between patients who underwent prerandomization basic (noncontrast computed tomography CT, CT angiography only) versus additional advanced imaging (computed tomography perfusion CTP imaging) and to determine the association of performance of prerandomization CTP imaging with clinical outcomes.
The HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) pooled patient-level data from randomized controlled trials comparing EVT with usual care for acute ischemic stroke due to anterior circulation large vessel occlusion. Good functional outcome, defined as modified Rankin Scale score 0 to 2 at 90 days, was compared between randomized patients with and without CTP baseline imaging. Univariable and multivariable binary logistic regression analysis was performed to determine the association of baseline CTP imaging and good functional outcome.
We analyzed 1348 patients 610 (45.3%) of whom underwent CTP prerandomization. The benefit of EVT compared with best medical management was maintained irrespective of the baseline imaging paradigm (90-day modified Rankin Scale score 0-2 in EVT versus control patients: with CTP: 46.0% (137/298) versus 28.9% (88/305), without CTP: 44.1% (162/367) versus 27.3% (100/366). Performance of CTP baseline imaging compared with baseline noncontrast CT and CT angiography only yielded similar rates of good outcome (odds ratio, 1.05 95% CI, 0.82-1.33, adjusted odds ratio, 1.04, 95% CI, 0.80-1.35).
Rates of good functional outcome were similar among patients in whom CTP was or was not performed, and EVT treatment effect in the 0- to 6-hour time window was similar in patients with and without baseline CTP imaging.
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